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dc.contributor.authorVarejao, Nathalia
dc.contributor.authorIbars Estiarte, Eva Irene
dc.contributor.authorLascorz, Jara
dc.contributor.authorColomina i Gabarrella, Neus
dc.contributor.authorTorres Rosell, Jordi
dc.contributor.authorReverter Cendrós, David
dc.date.accessioned2019-12-09T13:44:40Z
dc.date.available2019-12-09T13:44:40Z
dc.date.issued2018-06-15
dc.identifier.issn0261-4189
dc.identifier.urihttp://hdl.handle.net/10459.1/67685
dc.description.abstractModification of chromosomal proteins by conjugation to SUMO is a key step to cope with DNA damage and to maintain the integrity of the genome. The recruitment of SUMO E3 ligases to chromatin may represent one layer of control on protein sumoylation. However, we currently do not understand how cells upregulate the activity of E3 ligases on chromatin. Here we show that the Nse2 SUMO E3 in the Smc5/6 complex, a critical player during recombinational DNA repair, is directly stimulated by binding to DNA. Activation of sumoylation requires the electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5, which acts as a DNA sensor that subsequently promotes a stimulatory activation of the E3 activity in Nse2. Specific disruption of the interaction between the ARM of Smc5 and DNA sensitizes cells to DNA damage, indicating that this mechanism contributes to DNA repair. These results reveal a mechanism to enhance a SUMO E3 ligase activity by direct DNA binding and to restrict sumoylation in the vicinity of those Smc5/6‐Nse2 molecules engaged on DNA.
dc.description.sponsorshipWe thank Xiaolan Zhao for kindly providing the nse2‐CH allele. Members of our laboratories for discussions; Chris Lima and Luis Aragon for critical reading of the manuscript. This work was supported by grants from the “Ministerio de Economia y Competitividad” BFU2015‐66417‐P (MINECO/FEDER) to DR and grants BFU2015‐71308‐P and BFU2013‐50245‐EXP to JTR. NV acknowledges the support from the Science Without Borders (CNPq, Brazil).
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherEMBO Press
dc.relationMINECO/PN2013-2016/BFU2015-66417-P
dc.relationMINECO/PN2013-2016/BFU2015-71308-P
dc.relationMINECO/PN2013-2016/BFU2013-50245-EXP
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.15252/embj.201798306
dc.relation.ispartofEmbo Journal, 2018, vol. 37, núm. 12
dc.rights(c) Varejao, Nathalia et al., 2018
dc.subjectDNA repair
dc.subjectE3 ligase activity
dc.subjectNse2
dc.subjectSUMOylation
dc.subjectSmc5/6 complex
dc.titleDNA activates the Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2019-12-09T13:44:40Z
dc.identifier.idgrec028543
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.15252/embj.201798306


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